Evidence for adrenergic regulation of the coronary circulation will be sought using an anesthetized lamb model. Coronary blood flow, coronary vascular resistance and cardiac function will be determined and the relationship to alterations in oxygen and substrate metabolism (glucose and free fatty acids) will be assessed. The effects of direct electrical stimulation of the efferent sympathetic nerve supply to the heart will be examined and compared with alterations in sympathetic outflow engendered by cephalic ischemia. Responses before and following beta and alpha adrenergic blockade will be evaluated to identify receptor mechanisms which may be involved. The effects of the prostaglandins and angiotensins II on the coronary circulation and cardiac performance will be examined and pre-lung and post-lung infusions compared. The importance of prostaglandins in coronary regulation will be determined through the use of the blocking agent, indomethacin. Evidence for failure of neural transmitter mechanisms during sustained hemorrhagic hypotension will be sought and the relationship to progressive metabolic acidosis and hypercapnia will be determined. Dynamic compliance of the left ventricle will be studied in newborn and young lambs with a sonomicrometer system. The effects of sympathetic activity, hypoxia and acidosis will be assessed. BIBLIOGRAPHIC REFERENCES: Halloran, K.H., S.E. Downing: Inotropic responses to digoxin during hypoxia and autonomic blockade. Am. J. Physiol. 229: 309-313, 1975. Rieker, R.P., J.C. Lee and S.E. Downing: Positive inotropic effects of insulin upon piglet myocardium. Yale J. Biol. Med. 48: 353-360, 1976.